Specific differentiated cell types in culture will be developed and exploited to study the normal physiology and metabolic disorders of parent tissues. The nutritive, hormonal and extracellular matrix requirements for growth and function of several differentiated cell types have been or will be optimized. Bioeffectors, receptors, transducers and gene products will be purified and characterized by techniques of protein chemistry and molecular biology. Immunochemical and cDNA probes will be developed to study regulation of cell growth and specific gene products by hormones. Our basic premise is that factors discovered in culture that affect growth, function and differentiation are hormones involved in tissue physiology. The elucidation of these factors, their physiologic action and mechanism of action have practical importance in the management of metabolic disorders. The program consists of five projects devoted to these problems as well as a protein chemistry and molecular biology core support laboratories.